Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults

Brunner, Hermine I.; Bennett, Michael; Gulati, Gaurav; Abulaban, Khalid; Klein‐Gitelman, Marisa S.; Ardoin, Stacy P.; Tucker, Lori B.; Rouster‐Stevens, Kelly; Witte, David P.; Ying, Jun; Devarajan, Prasad

doi:10.3899/jrheum.161128

Cited by 39 publications

(48 citation statements)

References 42 publications

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“…Given the complexity of the pathogenesis of lupus nephritis, it is now widely accepted that a single urinary biomarker might not be powerful enough. Many groups have tried different approaches to address this [ 36 , 38 , 43 – 45 ]. In this study, we used a multiplex technology to simultaneously measure 10 candidate UBMs.…”

Section: Discussionmentioning

confidence: 99%

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

et al. 2020

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Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positive correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69–0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response.

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Section: Discussionmentioning

confidence: 99%

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

et al. 2020

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“…p values < 0.05 from 2-sided testing were considered statistically significant. To predict renal functional decline up to 12-months post baseline, urinary biomarker levels were tested in mixed model analyses as described previously [14]. Excel 2013 (Microsoft, Redmond, WA) and SAS 9.4 (SAS Institute, Cary, NC) programs were used for analysis.…”

Section: Discussionmentioning

confidence: 99%

“…At each visit, the systemic lupus erythematosus (SLE) disease activity index (SLEDAI-2 K) was completed, with additional calculation of its renal domain score (renal-SLEDAI; range, 0 to 16; 0 = no LN activity) as well as the renal domain score of the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology damage index (renal- SDI; range, 0 to 3; 0 = no LN damage) [14, 32]. Laboratory data recorded included serum creatinine, urine sediment, urine protein to creatinine ratio (UPCR) from a random spot urine sample, and the estimated glomerular filtration rate (GFR), using the modified Schwartz formula [33].…”

Section: Methodsmentioning

confidence: 99%

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

et al. 2018

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• Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis. • Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance. • Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.

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“…More recently, it has been reported that serum level of L-PGDS may represent a biomarker of kidney function ( White et al, 2015 ), pregnancy-induced hypertension ( Duan et al, 2016 ), and active lupus nephritis ( Brunner et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice

Song

Ricciotti

Liang

et al. 2018

J Pharmacol Exp Ther

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Prostaglandin (PG) D2 is formed by two distinct PGD synthases (PGDS): lipocalin-type PGDS (L-PGDS), which acts as a PGD2-producing enzyme and as extracellular lipophilic transporter, and hematopoietic PGDS (H-PGDS), a σ glutathione-S-transferase. PGD2 plays an important role in the maintenance of vascular function; however, the relative contribution of L-PGDS– and H-PGDS–dependent formation of PGD2 in this setting is unknown. To gain insight into the function played by these distinct PGDS, we assessed systemic blood pressure (BP) and thrombogenesis in L-Pgds and H-Pgds knockout (KO) mice. Deletion of L-Pgds depresses urinary PGD2 metabolite (PGDM) by ∼35%, whereas deletion of H-Pgds does so by ∼90%. Deletion of L-Pgds, but not H-Pgds, elevates BP and accelerates the thrombogenic occlusive response to a photochemical injury to the carotid artery. HQL-79, a H-PGDS inhibitor, further depresses PGDM in L-Pgds KO mice, but has no effect on BP or on the thrombogenic response. Gene expression profiling reveals that pathways relevant to vascular function are dysregulated in the aorta of L-Pgds KOs. These results indicate that the functional impact of L-Pgds deletion on vascular homeostasis may result from an autocrine effect of L-PGDS–dependent PGD2 on the vasculature and/or the L-PGDS function as lipophilic carrier protein.

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Urine Biomarkers to Predict Response to Lupus Nephritis Therapy in Children and Young Adults

Cited by 39 publications

References 42 publications

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus

Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice

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